Beyond Surgical Margins: Fully Mature Tertiary Lymphoid Structures (fmTLSs) Are Predictive Biomarkers for Local...

Area of Science:

• Oncology
• Immunology
• Pathology

Background:

• Soft-tissue sarcomas (STSs) are rare, heterogeneous cancers with poor prognoses.
• Tertiary lymphoid structures (TLSs) are linked to better outcomes in other cancers, but their role in STSs is unclear.
• This study examines the prognostic value of TLS characteristics in resected STSs.

Purpose of the Study:

• To investigate the prognostic relevance of TLS presence, maturity, location, and density in soft-tissue sarcomas.
• To correlate TLS features with survival outcomes and immune microenvironment profiles in STSs.

Main Methods:

• Retrospective analysis of 219 primary STS cases resected between 1990-2020.
• Assessment of TLS presence, distribution, density, and maturity (fully mature TLS-positive [fmTLS+] vs. negative [fmTLS-]) using immunohistochemistry (CD20, CD23).
• RNA sequencing on 126 samples to analyze immune microenvironment; survival analysis using Kaplan-Meier and Cox models.

Main Results:

• fmTLS presence significantly correlated with improved overall survival (OS) and cause-specific survival (p=0.012 and p=0.006, respectively).
• fmTLS+ tumors unexpectedly showed a higher rate of local recurrence (22.9% vs. 8.1%, p=0.002).
• High-density fmTLS+ STSs had a 2.68-fold increased risk of locoregional progression (p=0.009) and a high-immune phenotype (p<0.001).

Conclusions:

• Fully mature tertiary lymphoid structures (fmTLS) in STSs are associated with improved overall survival but a higher risk of local recurrence.
• fmTLS serves as a dual prognostic biomarker in STSs.
• Patients with fmTLS+ STSs may require tailored surveillance and adjuvant treatment strategies.